Hyperventilation-induced EEG changes in humans and their modulation by an anticonvulsant drug.
Surface-negative DC shifts, arising from depolarization of apical dendrites of cortical pyramidal cells, represent excitability of cortical neuronal networks. Hyperventilation, used in epilepsy diagnosis to provoke epileptiform discharges, is thought to increase excitability of neuronal tissue; correspondingly, hyperventilation produces negative DC shifts. Extreme negative DC shifts, accompanying epileptiform EEG patterns, have been observed in epileptic patients during hyperventilation. Anticonvulsants, supposed to dampen cortical excitability, should inhibit the development of overexcitability and, hence, also of pronounced negative DC shifts. The present study examined DC shifts induced by hyperventilation in healthy human subjects under the influence of the benzodiazepine, clonazepam, which is used as anticonvulsant. In a double-blind setting, 36 male student volunteers received 4.5 mg clonazepam or the equivalent amount of placebo. DC-EEG and respiration rate were measured during 3 periods each of 3 min: baseline, hyperventilation, and recovery. Compared to baseline, hyperventilation produced a negative DC shift of an average 36 +/- 8 microV under placebo conditions. Clonazepam reduced the hyperventilation-induced negativity to 13 +/- 5 microV. Negativity suppression became weakened with increasing blood plasma levels of the drug. Respiration depth and frequency, increasing under hyperventilation, did not differ among the groups. Clonazepam treatment gave rise to beta-waves and prevented the increase in alpha and theta activity that was found in placebo subjects during the recording period; this was only true, however, for low to moderate plasma concentrations of clonazepam. Results are consistent with the notion that a hyperventilation-induced increase in neuronal excitability can be measured by cortical DC shifts. The reduction of negative shifts under anticonvulsants might indicate dampening of cortical neuronal excitability which is intended by antiepileptic drugs.
Rockstroh
B
B
Department of Clinical and Physiological Psychology, Eberhard-Karls-Universität, Tübingen F.R.G.
D000328:Adult; D000927:Anticonvulsants / Q000494:pharmacology*; D002998:Clonazepam / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D004569:Electroencephalography; D006801:Humans; D006985:Hyperventilation / Q000503:physiopathology*; D008297:Male; D010919:Placebos; D012016:Reference Values; D012119:Respiration
D000927:Anticonvulsants; D010919:Placebos; D002998:Clonazepam